P1592: EFFECTS OF FETAL AND NEONATAL ALLOIMMUNE THROMBOCYTOPENIA (FNAIT) ON NEONATAL BIRTHWEIGHT: AN ANALYSIS USING SIBLING PAIRS
Authors: Margaret Mckelvy, James Bussel, Srishti Tyagi, Emilie Vander Haar
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from incompatibility between parental antigen types. Often, an HPA-1bb mother makes IgG anti-HPA-1a antibodies; these antibodies cross the placenta, accelerating fetal platelet destruction and inhibiting fetal platelet production causing severe thrombocytopenia which may result in intracranial hemorrhage. Recently, several studies reported decreased birthweight in FNAIT-affected male neonates. Aims: In a secondary analysis of a published study of FNAIT1,2 and of a questionnaire sent to mothers of children affected by FNAIT, we asked whether there was lower birthweight in FNAIT-affected neonates. Methods: Newborns of HPA-1bb mothers with FNAIT from our prior randomized trial (2001-2013) with and without antenatal management were included in this analysis of birthweights.1,2 Also, a questionnaire asking for self-reported data surveyed members of an organization called NAITbabies.org. In the clinical trial, treated neonates received either IVIG 1 g/kg x2/week (Group A) or IVIG 1 g/kg x1/week + prednisone 0.5 mg/kg/day (Group B). Antenatal management in the NAITbabies.org group was similar. For both groups, FNAIT-affected siblings antenatally treated were paired with their most recent untreated FNAIT-affected sibling for analysis using two-tailed t-tests. Birthweights were converted to percentiles from published normal controls to correct for differences in gestational age.3 The known effect of birth order on birthweight was accounted for by subtracting 130 g from each 2nd born child born at ≥ 38 weeks (100 g if < 38 weeks); for 2nd-3rd and 3rd-4th born pairs, 50 g was subtracted 50 g from each later born child born at ≥ 38 weeks (30 g < 38 weeks). Results: The 67 untreated siblings in the clinical trial were not small compared to controls; no gender differences were seen. However, the subsequent treated sibling had significantly higher birthweight percentiles than their untreated siblings (p < 0.00001). Accounting for the effect of birth order, the difference in percentile was still p = 0.0365. In the questionnaire cohort, babies were also not small and gender differences were not observed. Comparing untreated siblings to their treated siblings, treated siblings had greater percentiles (p < 0.00001). After correcting for birth order, treated siblings still had greater percentiles (p = 0.00224). In the clinical trial, no significant difference was found in birthweight percentiles in Group A vs Group B (Table 1). Summary/Conclusion: Untreated FNAIT-affected neonates were not small but antenatal management demonstrated increase size even when controlling for birth order. The clinical trial data were confirmed by the questionnaire data. The results suggest that anti-HPA-1a antibodies may have effects on fetal growth beyond the known effects on fetal platelets, perhaps by inducing placental inflammation. The lack of difference between Groups A and B suggest that the treatment effect was not due to IVIG and/or prednisone, as was also seen in published reports.1.Bussel J. A Trial of Antenatal Treatment of Alloimmune Thrombocytopenia. ClinicalTrials.gov identifier: NCT00194987. Updated November 7, 2018. Accessed November 2, 2022. 2.Lakkaraja M, Berkowitz RL, Vinograd CA, et al. Omission of fetal sampling in treatment of sub-sequent pregnancies in fetal-neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 2016;215:471.e1-9. 3.Fenton, T.R., Kim, J.H. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 13, 59 (2013). Keywords: Anti-platelet antibody, Platelet, Human platelet antigen, Thrombocytopenia